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FZJ-2018-02275

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Untersuchungen zur praktisch trägerfreien Radiohalogenierung rezeptorbindender 1,4-Benzodiazepine mit $^{18}$F, $^{75}$Br und $^{123}$I

Scholl, H. (Corresponding author)FZJ*

1983
Kernforschungsanlage Jülich, Verlag Jülich

Please use a persistent id in citations: http://hdl.handle.net/2128/17962

Report No.: Juel-1851

Abstract: Benzodiazepines, labelled with "organic" positron ( $^{11}$C, $^{18}$F, $^{75}$Br) or single-photon emitters ($^{123}$I), are potentially useful for mapping benzodiazepine receptor areas in-vivo by emissiontomography. In view of the reliability of $^{75}$Br (T$_{1/2}$ = 1.6 h) or $^{123}$I (T$_{1/2}$ = 13.3 h) labels it was a goal of this study to evaluate, synthesize and radiohalogenate benzodiazepines with high receptor affinity. For no-carrier-added (n. c. a.) regiospecific introduction of radiohalide, the triazene method was chosen. With regard for structure-activity-relationships which retain high ligand-receptor binding properties, eight basic 7-iodo-(or bromo-)-1,3-dihydro-5-(2-halophenyl)-2H-1,4-benzodiazepine-2-ones were synthesized. All compounds exhibit high receptor affinities, with inhibition constants below 2.7 nM. Four corresponding new piperidinyl-triazene precursors were prepared, and the conditions of the labelling reaction were optimized with $^{77}$Br by variation of solvents and the concentrations of triazene and acid. The influences of the addition of carrier bromide, crown ether, phase transfer catalyst, or water on the radiochemical yield were investigated. At optimum reaction conditions, using 7 umoles of triazene and 21 umoles of CH$_{3}$SO$_{3}$H in 0.2 ml of toluene, one [$^{123}$I]- and four different [$^{77}$Br]-benzodiazepines were obtained with radiochemical yields of 41-64 %. $^{18}$F, however, did not react under these conditions. These methods were developed to allow routine production of radiohalogenated compounds in a 4GBq 100o mCi) scale. In one run, 52o MBq (14 mCi) of the benzodiazepine [$^{75}$Br]-BFB were prepared at a specific activity of 63o TBq (17 000 Ci)/mmol (72o TBq/mmol with $^{77}$Br). The appropriate factors of dilution with inactive BFB are 2oo with 75Br and 3 with $^{77}$Br. Using a simple apparatus, the total synthesis requires only one hour. In addition to the production of the radiopharmaceuticals, the major inactive side-products of the triazene decomposition were separated and identified by spectroscopic methods. The reaction mechanism involved is discussed, as well as the spectroscopic and chromatographic behaviour of all synthesized benzodiazepines.

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Contributing Institute(s):

1. Publikationen vor 2000 (PRE-2000)

Research Program(s):

1. 899 - ohne Topic (POF3-899) (POF3-899)

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